Metaxalone's mechanism of action in humans has not been fully established, but it may be due to general central nervous system depression. Unlike other muscle relaxants, it does not appear to act directly on skeletal muscle or at the neuromuscular junction. Its effects are thought to be mediated through the central nervous system, possibly by inhibiting polysynaptic reflexes. The exact molecular target of metaxalone remains unclear, and it is not known to interact with specific receptors or enzymes.

In vitro, metaxalone's muscle relaxant activity is not well-characterized, as its mechanism of action is believed to be central rather than direct on muscle tissue. It is not known to inhibit specific enzymes, modulate receptor activity, or affect cellular signaling pathways in a well-defined manner. Its primary application is in clinical use for muscle relaxation, and in vitro studies have focused on its chemical properties and metabolism rather than pharmacological activity.

In vivo, metaxalone is an effective muscle relaxant used to relieve pain and discomfort associated with acute musculoskeletal conditions. It is used as an adjunct for the treatment of acute skeletal muscle pain caused by strains, sprains, and other musculoskeletal conditions. It is commonly used for acute low back pain. Metaxalone is effective in relieving pain and improving function in patients with acute musculoskeletal pain.

In vitro assays for metaxalone are primarily related to its chemical properties and metabolism rather than pharmacological activity. Cytotoxicity assays using mammalian cell lines (e.g., HepG2, CHO) may be performed for safety assessment. The compound's metabolism can be studied using liver microsomes or hepatocyte cultures to identify metabolites and metabolic pathways. However, specific protocols for receptor binding or enzyme inhibition assays are not standard for this compound.

In vitro cell-based assays for metaxalone are not commonly reported, as its mechanism of action is central rather than direct on cells. If conducted, they would assess its potential for cytotoxicity rather than therapeutic activity. Human cell lines could be exposed to the compound, and cell viability would be measured. However, such assays are not typically performed for this compound as it is a clinically used muscle relaxant.

In vivo animal studies for metaxalone were conducted during its development as a muscle relaxant. Typical protocols involve administering the compound to rodents and assessing its effects on muscle tone, motor coordination, and pain responses. The compound's efficacy in relieving muscle spasms and pain is evaluated using standard animal models of musculoskeletal pain. However, specific detailed protocols are not extensively detailed in the available literature.

Absorption, Distribution and Excretion
The absolute bioavailability of methadone in Skelaxin tablets is unknown. Metadhadone is metabolized in the liver and excreted in the urine as an unidentified metabolite. 800 L 68 ± 50 L/h [Subject taking one 400 mg tablet on an empty stomach] 66 ± 51 L/h [Subject taking two 400 mg tablets on an empty stomach] Although the plasma protein binding and absolute bioavailability of methadone are unknown, its apparent volume of distribution (V/F ~ 800 L) and lipophilicity (log P = 2.42) indicate extensive distribution in tissues. Metadhadone is metabolized in the liver and excreted in the urine as an unidentified metabolite. After oral administration of 400 mg methadone on an empty stomach, peak plasma concentrations are reached in approximately 3 hours. Thereafter, methadone concentrations decrease logarithmically, with a terminal half-life of 9.0 ± 4.8 hours. Increasing the methadone dose from 400 mg to 800 mg resulted in a roughly proportional increase in methadone exposure, as evidenced by peak plasma concentration (Cmax) and area under the curve (AUC). Dose-proportioning relationships at doses exceeding 800 mg have not been investigated. The absolute bioavailability of methadone is unknown. Metabolites/Metabolic Substances: Likely metabolized in the liver. Biotransformation… has been studied in dogs and humans. The major metabolite, 5-(3-methyl-5-carboxyphenoxymethyl)-2-oxazolidinone, is excreted in urine and feces; this metabolite is also present in urine as an ester glucuronide. Ether bond cleavage yields 3,5-xylenol and 5-hydroxymethyloxazolidinone. The oxazolidinone ring is stable in mammals. In humans and dogs, 5-(5-carboxy-3-methylphenoxymethyl)-2-oxazolidinone is formed, and in humans and dogs, 3,5-dimethylphenol is formed. (Data from table) Metaxadone is metabolized in the liver and excreted in the urine as unidentified metabolites. Biological half-life: 9.2 (± 4.8) hours; terminal half-life: 9.0 ± 4.8 hours.
Metaxalone is absorbed from the gastrointestinal tract after oral administration. It is metabolized in the liver, primarily through hydroxylation and conjugation. The compound has a half-life of approximately 5-6 hours in humans. It is excreted primarily in urine as metabolites. The pharmacokinetics of metaxalone may be affected by food intake, and it is typically recommended to be taken with food to improve tolerability.

Hepatotoxicity
According to the product information leaflet, methadone may cause jaundice, but there are no specific case reports of methadone-induced hepatotoxicity in the literature, nor are there any prospective trials routinely monitoring transaminase levels. Given its long history of use, methadone does not appear to have significant hepatotoxicity. Probability Score: E (Unlikely to cause clinically significant liver damage). Drug Category: Muscle Relaxant. Interactions
When methadone is used in combination with other central nervous system depressants (including alcohol), there may be an additive effect of central nervous system depression. Caution should be exercised when methadone is used in combination with other depressants to avoid overdose.
Metaxalone is generally well-tolerated, but it can cause side effects including drowsiness, dizziness, headache, and gastrointestinal disturbances. It is contraindicated in patients with significant hepatic or renal impairment. As with other central nervous system depressants, it may cause sedation and should be used with caution in patients who operate machinery or drive. Metaxalone is not recommended for use in pregnancy unless clearly needed.

https://en.wikipedia.org/wiki/Metaxalone

Metadaxone is an aromatic ether. Metadaxone is a moderate to potent muscle relaxant used to treat musculoskeletal pain caused by strains, sprains, and other musculoskeletal disorders. It is marketed by King's Pharmaceuticals under the brand name Skelaxin®. Its primary mechanism of action is believed to be central nervous system depression. Metadaxone has few side effects and is available in 800 mg scored tablets. Metadaxone is a muscle relaxant. The physiological action of metadaxone is achieved through centrally mediated muscle relaxation. Metadaxone is a centrally acting skeletal muscle relaxant that has been used for over 40 years. No elevation of serum transaminases or clinically significant liver damage has been observed during metadaxone treatment. There are reports and data regarding the effects of metadaxone in C. elegans. Metadaxone is an oxazolidinone with central skeletal muscle relaxant activity. Although the exact mechanism of action of metadaxone is not fully understood, it may be related to central nervous system depression. Metadalidomide has no direct effect on the contraction mechanism of skeletal muscle, motor endplates, or nerve fibers. Drug Indications For the treatment of spasticity caused by painful peripheral musculoskeletal disorders and upper motor neuron syndrome. FDA Label Mechanism of Action The mechanism of action of metadalidomide in humans is not fully understood, but it may be related to central nervous system depression. Metadalidomide is a central nervous system depressant with sedative and skeletal muscle relaxant effects. The exact mechanism of action of this drug is unknown. Oral metadalidomide has a weak skeletal muscle relaxant effect, which may be related to its sedative effect. This drug does not directly relax skeletal muscle and, unlike neuromuscular blocking agents, it does not inhibit nerve conduction, neuromuscular transmission, or muscle excitability. The mechanism of action of metadalidomide in humans is not fully understood, but it may be related to central nervous system depression. Metadalidomide has no direct effect on the contraction mechanism of skeletal muscle, motor endplates, or nerve fibers.

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Therapeutic Use
Metasadone may be used as an adjunct to rest, physical therapy, analgesia, and other measures to relieve discomfort caused by acute painful musculoskeletal disorders. /US product label contains/

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Drug Warnings
The most common adverse reactions to metasadone include somnolence, dizziness, headache, nervousness or irritability, nausea, vomiting, and gastrointestinal upset. Other adverse reactions include confusion, anorexia, dry mouth, and urinary retention. There have also been reports of exacerbation of tonic-clonic (grand mal) seizures. Hypersensitivity reactions and rash (with or without pruritus) have been reported in patients treated with metasadone. Rarely, anaphylactic reactions, leukopenia, hemolytic anemia, and jaundice have occurred. Abnormal liver function tests have been reported in patients treated with metasadone, such as elevated serum AST (SGOT), ALT (SGPT), alkaline phosphatase, and bilirubin levels, as well as increased sulfobromophthalein sodium (BSP) retention and increased thymol turbidity. Although a causal relationship with methadone has not been established, rare cases of nephrotoxicity and proteinuria have occurred during treatment with this drug; pyuria and kidney stones have been reported. The safety and efficacy of methadone in children aged 12 years and under have not been established; therefore, this drug should not be given to children in this age group. Patients should be informed that methadone may impair their ability to perform dangerous activities requiring mental alertness or physical coordination, such as operating machinery or driving motor vehicles. Furthermore, patients should be informed that there may be an additive effect of central nervous system depressant effects when this drug is taken concomitantly with other central nervous system depressants (including alcohol). Metadhadone should be used with caution in elderly patients and patients with hepatic or renal impairment. For patients with a history of liver injury, liver function tests should be performed regularly during methadone treatment. This drug is contraindicated in patients with severely impaired hepatic or renal function, known hypersensitivity to this drug or any component of its preparations, or a history of drug-induced, hemolytic, or other types of anemia. For more complete (8) drug warnings regarding methadone, please visit the HSDB records page.

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Pharmacodynamics
Metadalone is a skeletal muscle relaxant used in conjunction with rest, physical therapy, and other measures to relieve discomfort caused by acute painful musculoskeletal disorders. The mechanism of action of this drug is not fully understood, but may be related to its sedative effect. Metadalone does not directly relax tense skeletal muscles in the human body.
Metaxalone is a skeletal muscle relaxant used for the treatment of acute musculoskeletal pain. It is available as an oral medication and is commonly used for acute low back pain. Its mechanism of action is not fully understood but may involve central nervous system depression. Metaxalone is effective in relieving pain and improving function in patients with acute musculoskeletal conditions. This product is for human therapeutic use.

C12H15NO3

221.2524

221.105

1665-48-1

Metaxalone-d3;1192812-66-0;Metaxalone-d6;1189944-95-3

15459

White to almost white crystalline powder
Crystals from ethyl acetate

1.1±0.1 g/cm3

453.6±14.0 °C at 760 mmHg

121-123ºC

228.2±20.1 °C

0.0±1.1 mmHg at 25°C

1.525

2.42

1

3

3

16

247

0

O1C(N([H])C([H])([H])C1([H])C([H])([H])OC1C([H])=C(C([H])([H])[H])C([H])=C(C([H])([H])[H])C=1[H])=O

IMWZZHHPURKASS-UHFFFAOYSA-N

InChI=1S/C12H15NO3/c1-8-3-9(2)5-10(4-8)15-7-11-6-13-12(14)16-11/h3-5,11H,6-7H2,1-2H3,(H,13,14)

5-[(3,5-dimethylphenoxy)methyl]-1,3-oxazolidin-2-one

AHR438; NSC170959; AHR-438; NSC-170959; AHR 438;NSC 170959 Metaxalone; Skelaxin; Methaxalonum; Metaxalon; Zorane; AHR 438; 3B2-1432; I06-0370;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~451.98 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (11.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (11.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)